Gemcitabine/cisplatin versus 5-fluorouracil/mitomycin C chemoradiotherapy in locally advanced pancreatic cancer: a retrospective analysis of 93 patients

<p>Abstract</p> <p>Background</p> <p>Despite of a growing number of gemcitabine based chemoradiotherapy studies in locally advanced pancreatic cancer (LAPC), 5-fluorouracil based regimens are still regarded to be standard and the debate of superiority between the two drugs is going on. The aim of this retrospective analysis was to evaluate the effect of two concurrent chemoradiotherapy regimens using 5-fluorouracil or gemcitabine to compare their effect and tolerance.</p> <p>Methods</p> <p>We have performed a single centre retrospective analysis of 93 patients treated with conventionally fractionated radiotherapy of 55.8 Gray using either concurrent 5-fluorouracil, 1 g/m² on days 1-5 and 29-33 of radiotherapy and 10 mg/m² of mitomycin C on day 1, 29 of radiotherapy (FM group, 35 patients) versus gemcitabine (300 mg/m²) and cisplatin, (30 mg/m²) on days 1, 8, 22, and 29 (GC group, 58 patients). Primary endpoint was the median overall survival (OS) rate.</p> <p>Results</p> <p>The median OS rate was 12.7 months in the GC group and 9.7 months in the FM group. The 1-year OS rate was 53% versus 40%, respectively (p = 0.009). GC led to more grade 3 leukocytopenia and thrombocytopenia than FM, but not to more grade 4 myelosuppression. Thrombocytopenia was the most frequently observed grade 4 toxicity in both groups (11% after FM versus 12% after GC). No grade 3/4 febrile neutropenia was observed. Grade 3 nausea was more common in the FM group (20% versus 9%) and grade 4 nausea was observed in one patient per group only.</p> <p>Conclusions</p> <p>GC was superior to FM for overall survival and both regimens were similar in terms of tolerance. We conclude that GC leads to encouraging results and that the use of FM for chemoradiotherapy in LAPC cannot be recommended without concerns.</p

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New Data on Pancreatic Cancer In pancreatic cancer there is a marked discrepancy between the recorded R0 resection rates and the long-term clinical outcome. Therefore, it seems to be necessary to find additional parameters that will be of more prognostic value here. Differences in how the R classification is applied within the studies are conspicuous. It would seem important to examine standards in histopathological preparation and to return to the `classical' R classification and, if appropriate, in line with experiences in rectum cancer, to introduce a `circumferential resection margin'. To obtain optimum long-term survival, a distance of >1.0 mm or even >1.5 mm between tumor and resection margin is required. In too few patients with vascular invasion is the tumor properly removed surgically, even though infiltration of the portal vein or the superior mesenteric vein is not an exclusion criterion according to the S3 guideline. An improvement in the quality of treatment might be achieved by establishing `high-volume' pancreas centers. The value of perioperative radiochemotherapy (RCT) is currently being examined in several large studies. Adjuvant chemotherapy is standard and is well established in routine clinical practice

CD8+ and Regulatory T cells Differentiate Tumor Immune Phenotypes and Predict Survival in Locally Advanced Head and Neck Cancer

Background: The tumor immune status “inflamed”, “immune excluded”, and “desert” might serve as a predictive parameter. We studied these three cancer immune phenotypes while using a simple immunohistochemical algorithm. Methods: Pre-treatment tissue samples of 280 patients with locally advanced HNSCC treated with radiochemotherapy were analyzed. A double staining of CD8+ cytotoxic T cells (CTL) and FoxP3+ (Treg) was performed and the cell density was evaluated in the intraepithelial and stromal compartment of the tumor. Results: The classification of tumors as “immune desert” when stromal CTL were ≤ 50 cells/mm2, “inflamed” when intraepithelial CTL were > 500 cells/mm2, and as “excluded” when neither of these definitions met these cut off values allowed the best discrimination regarding overall survival. These groups had median OS periods of 37, 61, and 85 months, respectively. In “immune desert” and “immune excluded” tumors high Treg tended to worsen OS, but in “inflamed” tumors high Treg clearly improved OS. Conclusions: We propose that, in locally advanced HNSCC, the tumor immune state “inflamed”, “immune excluded”, and “immune desert” can be defined by intraepithelial and stromal CTL. Tregs can further subdivide these groups. The opposing effects of Tregs in the different groups might be the reason for the inconsistency of Tregs prognostic values published earlier

Long-Term Experience of Chemoradiotherapy Combined with Deep Regional Hyperthermia for Organ Preservation in High-Risk Bladder Cancer (Ta, Tis, T1, T2).

BackgroundThe aim of this study was to evaluate the efficacy and safety of chemoradiotherapy (RCT) combined with regional deep hyperthermia (RHT) of high-risk bladder cancer after transurethral resection of bladder tumor (TUR-BT).Materials and methodsBetween 1982 and 2016, 369 patients with pTa, pTis, pT1, and pT2 cN0-1 cM0 bladder cancer were treated with a multimodal treatment after TUR-BT. All patients received radiotherapy (RT) of the bladder and regional lymph nodes. RCT was administered to 215 patients, RCT + RHT was administered to 79 patients, and RT was used in 75 patients. Treatment response was evaluated 4-6 weeks after treatment with TUR-BT.ResultsComplete response (CR) overall was 83% (290/351), and in treatment groups was RT 68% (45/66), RCT 86% (178/208), and RCT + RHT 87% (67/77). CR was significantly improved by concurrent RCT compared with RT (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.05-5.12; p = .037), less influenced by hyperthermia (OR, 2.56; 95% CI, 0.88-8.00; p = .092). Overall survival (OS) after RCT was superior to RT (hazard ratio [HR], 0.7; 95% CI, 0.50-0.99; p = .045). Five-year OS from unadjusted Kaplan-Meier estimates was RCT 64% versus RT 45%. Additional RHT increased 5-year OS to 87% (HR, 0.32; 95% CI, 0.18-0.58; p = .0001). RCT + RHT compared with RCT showed a significantly better bladder-preservation rate (HR, 0.13; 95% CI, 0.03-0.56; p = .006). Median follow-up was 71 months. The median number of RHT sessions was five.ConclusionThe multimodal treatment consisted of a maximal TUR-BT followed by RT; concomitant platinum-based chemotherapy combined with RHT in patients with high-grade bladder cancer improves local control, bladder-preservation rate, and OS. It offers a promising alternative to surgical therapies like radical cystectomy.Implications for practiceRadical cystectomy with appropriate lymph node dissection has long represented the standard of care for muscle-invasive bladder cancer in medically fit patients, despite many centers reporting excellent long-term results for bladder preserving strategies. This retrospective analysis compares different therapeutic modalities in bladder-preservation therapy. The results of this study show that multimodal treatment consisting of maximal transurethral resection of bladder tumor followed by radiotherapy, concomitant platinum-based chemotherapy combined with regional deep hyperthermia in patients with Ta, Tis, T1-2 bladder carcinomas improves local control, bladder-preservation rate, and survival. More importantly, these findings offer a promising alternative to surgical therapies like radical cystectomy. The authors hope that, in the future, closer collaboration between urologists and radiotherapists will further improve treatments and therapies for the benefit of patients

Deep Learning for Cancer Prognosis Prediction Using Portrait Photos by StyleGAN Embedding

Survival prediction for cancer patients is critical for optimal treatment selection and patient management. Current patient survival prediction methods typically extract survival information from patients' clinical record data or biological and imaging data. In practice, experienced clinicians can have a preliminary assessment of patients' health status based on patients' observable physical appearances, which are mainly facial features. However, such assessment is highly subjective. In this work, the efficacy of objectively capturing and using prognostic information contained in conventional portrait photographs using deep learning for survival predication purposes is investigated for the first time. A pre-trained StyleGAN2 model is fine-tuned on a custom dataset of our cancer patients' photos to empower its generator with generative ability suitable for patients' photos. The StyleGAN2 is then used to embed the photographs to its highly expressive latent space. Utilizing the state-of-the-art survival analysis models and based on StyleGAN's latent space photo embeddings, this approach achieved a C-index of 0.677, which is notably higher than chance and evidencing the prognostic value embedded in simple 2D facial images. In addition, thanks to StyleGAN's interpretable latent space, our survival prediction model can be validated for relying on essential facial features, eliminating any biases from extraneous information like clothing or background. Moreover, a health attribute is obtained from regression coefficients, which has important potential value for patient care

Quality assurance and long-term stability of a novel 3-in-1 X-ray system for brachytherapy

Purpose A novel, mobile 3-in-1 X-ray system featuring radiography, fluoroscopy, and cone-beam computed tomography (CBCT) has been launched for brachytherapy recently. Currently, there is no quality assurance (QA) procedure explicitly applicable to this system equipped with innovative technologies such as dynamic jaws and motorized lasers. We developed a dedicated QA procedure and, based on its performance for a duration of 6 months, provide an assessment of the device's stability over time. Methods With the developed QA procedure, we assessed the system's planar and CBCT-imaging performance by investigating geometric accuracy, CT-number stability, contrast-noise-ratio, uniformity, spatial resolution, low-contrast detectability, dynamic range, and X-ray exposure using dedicated phantoms. Furthermore, we evaluated geometric stability by using the flexmap-approach and investigated the device's laser- and jaw-positioning accuracy with an in-house test phantom. CBCT- and planar-imaging protocols for pelvis, breast, and abdomen imaging were examined. Results Planar- and CBCT-imaging performances were widely stable with a geometric accuracy ≤1 mm, CT-number stability of up to 46 HU, and uniformity variations of up to 48 HU over time. For planar imaging, low-contrast detectability and dynamic range exceeded current recommendations. Although geometric stability was considered tolerable, partly substantial positioning inaccuracies of up to more than 120 mm and −13 mm were obtained for lasers and jaws, respectively. X-ray exposure showed small variations of ≤0.56 μGy and ≤0.76 mGy for planar- and CBCT-imaging, respectively. The conductance of the QA procedure allowed a smooth evaluation of the system's overall performance. Conclusion We developed a QA workflow for a novel 3-in-1 X-ray system allowing to assess the device's imaging and hardware performance. The system showed in general a reasonable imaging performance and stability over time, whereas improvements regarding laser and jaw accuracy are strictly required

Immune biological rationales for the design of combined radio- and immunotherapies

Abstract Cancer immunotherapies are promising treatments for many forms of cancer. Nevertheless, the response rates to, e.g., immune checkpoint inhibitors (ICI), are still in low double-digit percentage. This calls for further therapy optimization that should take into account combination of immunotherapies with classical tumor therapies such as radiotherapy. By designing multimodal approaches, immune modulatory properties of certain radiation schemes, additional immune modulation by immunotherapy with ICI and hyperthermia, as well as patient stratification based on genetic and immune constitutions have to be considered. In this context, both the tumor and its microenvironment including cells of the innate and adaptive immune system have to be viewed in synopsis. Knowledge of immune activation and immune suppression by radiation is the basis for well-elaborated addition of certain immunotherapies. In this review, the focus is set on additional immune stimulation by hyperthermia and restoration of an immune response by ICI. The impact of radiation dose and fractionation on immune modulation in multimodal settings has to be considered, as the dynamics of the immune response and the timing between radiotherapy and immunotherapy. Another big challenge is the patient stratification that should be based on matrices of biomarkers, taking into account genetics, proteomics, radiomics, and “immunomics”. One key aim is to turn immunological “cold” tumors into “hot” tumors, and to eliminate barriers of immune-suppressed or immune-excluded tumors. Comprehensive knowledge of immune alterations induced by radiation and immunotherapy when being applied together should be utilized for patient-adapted treatment planning and testing of innovative tumor therapies within clinical trials